In vivo ectopic chondrogenesis of BMSCs directed by mature chondrocytes

Liu, Xia; Sun, Huai; Yan, Dongpeng; Zhang, Lu; Lv, Xiufang; Liu, Tianyi; Zhang, Wenjie; Liu, Wei; Cao, Yilin; Zhou, Guangdong

doi:10.1016/j.biomaterials.2010.08.052

Cited by 145 publications

(112 citation statements)

References 44 publications

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“…We found that sorted and expanded iPSCderived cells seeded in agarose were effective at filling the defect with cartilaginous matrix that integrated well with the surrounding cartilage. Interestingly, matrix production by iPSCs was enhanced near the native cartilage surface, possibly due to paracrine signals from chondrocytes (46). The agarose constructs with cells contributed to a defect repair that far exceeded native cartilage healing and the cell-free agarose group, which provides a control for the effects of friction.…”

Section: Discussionmentioning

confidence: 99%

Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells

Diekman

Christoforou

Willard

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

234

250

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The development of regenerative therapies for cartilage injury has been greatly aided by recent advances in stem cell biology. Induced pluripotent stem cells (iPSCs) have the potential to provide an abundant cell source for tissue engineering, as well as generating patient-matched in vitro models to study genetic and environmental factors in cartilage repair and osteoarthritis. However, both cell therapy and modeling approaches require a purified and uniformly differentiated cell population to predictably recapitulate the physiological characteristics of cartilage. Here, iPSCs derived from adult mouse fibroblasts were chondrogenically differentiated and purified by type II collagen (Col2)-driven green fluorescent protein (GFP) expression. Col2 and aggrecan gene expression levels were significantly up-regulated in GFP+ cells compared with GFP− cells and decreased with monolayer expansion. An in vitro cartilage defect model was used to demonstrate integrative repair by GFP+ cells seeded in agarose, supporting their potential use in cartilage therapies. In chondrogenic pellet culture, cells synthesized cartilagespecific matrix as indicated by high levels of glycosaminoglycans and type II collagen and low levels of type I and type X collagen. The feasibility of cell expansion after initial differentiation was illustrated by homogenous matrix deposition in pellets from twicepassaged GFP+ cells. Finally, atomic force microscopy analysis showed increased microscale elastic moduli associated with collagen alignment at the periphery of pellets, mimicking zonal variation in native cartilage. This study demonstrates the potential use of iPSCs for cartilage defect repair and for creating tissue models of cartilage that can be matched to specific genetic backgrounds.chondrocyte | bone morphogenetic proteins | transforming growth factor-beta | cartilage micromechanics | cartilage regeneration

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Section: Discussionmentioning

confidence: 99%

Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells

Diekman

Christoforou

Willard

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

234

250

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“…For example, it was reported that cartilage explants secreted TGF-b for up to 14 days, and soluble factors derived from cartilage explants were able to upregulate SOX9 gene expression and type II collagen synthesis in MSCs. 14 Similar studies confirmed that soluble factors derived from chondrocytes were able to upregulate chondrogenic gene markers and matrix production by MSCs, 15,16 and reduce hypertrophic markers in MCSs. 14,17 However, the chondrogenesis induction reported via chondrocyte-conditioned media showed only moderate type II collagen gene upgregulation over control media and predominately type I collagen matrix accumulation.…”

mentioning

confidence: 64%

“…While coculture of these two populations has been reported, [14][15][16][17][18][19] results have been mixed, and there are no reports of zonal coculture models. A clear trend has not been established on the influence or the mechanisms of influence between these two cell populations.…”

mentioning

confidence: 99%

Engineering Superficial Zone Chondrocytes from Mesenchymal Stem Cells

Coates

Fisher

2014

Tissue Engineering Part C: Methods

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Recent cartilage engineering efforts have focused on development of zonally organized tissue. However, there remains a need for protocols that differentiate progenitor populations into chondrocytes of zonal phenotype. Here, we evaluate the potential of coculture of bovine mesenchymal stem cells (MSCs) and zonal explants of bovine cartilage tissue to drive MSC differentiation to chondrocytes with the superficial zone phenotype. Two coculture systems were set up: one between alginate encapsulated MSCs and superficial zone cartilage explants, and one between MSCs and middle/deep zone cartilage explants. Chondrogenic and superficial zone markers were monitored over a 21-day differentiation period via gene and protein expression. A control conditioned media study was used to determine the impact of communication via soluble factors between cell populations during differentiation. At day 21, results show superficial zone explant coculture without transforming-growth factor b3 supplementation induces upregulation of chondrogenic gene expression markers SOX9 and type II collagen 3.4-fold and 11.4-fold, respectively, over standard chondrogenic control media. Further, coculture of MSCs and superficial zone explants can be used to upregulate mRNA expression of the superficial zone marker proteoglycan-4 in MSCs (1.75-fold over chondrogenic control at day 21), indicating the superficial zone chondrocyte phenotype. Gene expression data show middle/deep zone explant and MSC coculture did not induce the chondrogenesis observed in superficial zone explant coculture. Likewise, poor chondrogenesis was observed in all conditioned media groups. Results highlight the importance of superficial zone cartilage and cells in guiding stem cell fate and regulating differentiation of MSCs to chondrocytes of the superficial zone type.

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“…230 In cartilage, mature chondrocytes are demonstrated to secrete TGF-2, BMP-2, and IGF-1 to direct and enhance MSC chondrogenesis with substantial increase in tissue volume, mass, and ECM production. 231 The special case of PRP Another promising strategy based on the use of GFs for stimulation of bone, cartilage, and osteochondral healing is through the use of PRP. The implementation of an autologous technology represents a new translational procedure acting as an alternative to the limitations observed with the current TE and regenerative medicine cell-based approaches.…”

Section: From Single To Multiple Bioactive Factor Delivery For Skeletmentioning

confidence: 99%

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

Santo

Gomes²,

Mano³

et al. 2013

Tissue Engineering Part B: Reviews

105

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The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors.

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In vivo ectopic chondrogenesis of BMSCs directed by mature chondrocytes

Cited by 145 publications

References 44 publications

Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells

Cartilage tissue engineering using differentiated and purified induced pluripotent stem cells

Engineering Superficial Zone Chondrocytes from Mesenchymal Stem Cells

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

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